Abstract:Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER)
located
phase I enzyme, plays a vital role in the metabolism of various endogenous
and exogenous substances, and is regarded as an important target for
the design of prodrugs. Unfortunately, superior highly selective ER
targeting fluorescent probes for monitoring of CES2 are not currently
available. Herein, we report an ER targeting CES2 selective and sensitive
ratiometric fluorescent probe ERNB based on the ER localizing
group p-toluenesulfonamide. ERNB… Show more
“…James and Ma et al. designed an endoplasmic reticulum (ER) targeting ratiometric fluorescent probe 15 which can sensitively detect carboxylesterase 2 (CES2) and has an excellent ER‐targeting ability (Figure c) . P‐toluenesulfonamide was introduced to achieve the ER‐targeting ability of probe 15.…”
Section: Classification and Functions Of Cesssupporting
As the most important members of serine esterase hydrolase superfamily, mammalian carboxylesterases (CESs) are widely distributed in various tissues like liver, intestine, lung and kidney. Many physiological processes require the hydrolysis of CES with a variety of endogenous and exogenous ester drugs and environmental poisons. So, developing the methods that can detect CESs activity is of great significance. In last decades, huge breakthrough has been made in the development of specific detection technologies including chromatography, quantitative reverse transcription polymerase chain reaction (qRT-PCR), proteomics and western blotting. However, these traditional methods for CESs detection have little effect on the spatiotemporal distribution and in situ activity of CES in living cells and in vivo. Compared with that, fluorogenic methods have been developed for real-time monitoring CESs in biological environments. In this review, we summarized the recent reported CESs probes. The designing strategies as well as their applications are reviewed. We hope this review will inspire the development of novel specific CESs fluorescent probes.
“…James and Ma et al. designed an endoplasmic reticulum (ER) targeting ratiometric fluorescent probe 15 which can sensitively detect carboxylesterase 2 (CES2) and has an excellent ER‐targeting ability (Figure c) . P‐toluenesulfonamide was introduced to achieve the ER‐targeting ability of probe 15.…”
Section: Classification and Functions Of Cesssupporting
As the most important members of serine esterase hydrolase superfamily, mammalian carboxylesterases (CESs) are widely distributed in various tissues like liver, intestine, lung and kidney. Many physiological processes require the hydrolysis of CES with a variety of endogenous and exogenous ester drugs and environmental poisons. So, developing the methods that can detect CESs activity is of great significance. In last decades, huge breakthrough has been made in the development of specific detection technologies including chromatography, quantitative reverse transcription polymerase chain reaction (qRT-PCR), proteomics and western blotting. However, these traditional methods for CESs detection have little effect on the spatiotemporal distribution and in situ activity of CES in living cells and in vivo. Compared with that, fluorogenic methods have been developed for real-time monitoring CESs in biological environments. In this review, we summarized the recent reported CESs probes. The designing strategies as well as their applications are reviewed. We hope this review will inspire the development of novel specific CESs fluorescent probes.
“…Indeed, genetic abnormalities and the aberrant inflammatory microenvironment of the liver respond to the induction of ER stress in macrophages of ALI. Abundant genetic studies have revealed primary aberrances in several ER homeostasis-associated genes, such as carboxylesterase 2, sirtuin 1, and interferon regulatory factor 3, in AKI patients [31][32][33]. Combined with preceding studies from our team, ARRB1 may be a potential ER homeostasis-associated gene.…”
Acute liver injury (ALI) caused by multiple inflammatory responses is a monocyte-/macrophage-mediated liver injury that is associated with high morbidity and mortality. Liver macrophage activation is a vital event that triggers ALI. However, the mechanism of liver macrophage activation has not been fully elucidated. This study examined the role of β-arrestin1 (ARRB1) in wild-type (WT) and ARRB1-knockout (ARRB1-KO) mouse models of ALI induced by lipopolysaccharide (LPS), and ARRB1-KO mice exhibited more severe inflammatory injury and liver macrophage activation compared to WT mice. We found that LPS treatment reduced the expression level of ARRB1 in Raw264.7 and THP-1 cell lines, and mouse primary hepatic macrophages. Overexpression of ARRB1 in Raw264.7 and THP-1 cell lines significantly attenuated LPS-induced liver macrophage activation, such as transformation in cell morphology and enhanced expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), while downregulation of ARRB1 by small interfering RNA and ARRB1 deficiency in primary hepatic macrophages both aggravated macrophage activation. Moreover, overexpression of ARRB1 suppressed LPS-induced endoplasmic reticulum (ER) stress in liver macrophages, and inhibition of ER stress impeded excessive hepatic macrophage activation induced by downregulation of ARRB1. Our data demonstrate that ARRB1 relieves LPS-induced ALI through the ER stress pathway to regulate hepatic macrophage activation and that ARRB1 may be a potential therapeutic target for ALI.
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